We have previously provided the first evidence for a potential molecular link between the egg granuloma and activation of fibroblasts in the etiology of hepatic fibrosis in schistosomiasis. We now isolate and characterize the fibroblast stimulating factos derived from granulomas and from schistosomal eggs. The goal of this study is to provide a basis for detecting the factors independent of their biological activity, thereby permitting subsequent basic and clinical investigations of the immunology and cell biology of fibroplasia in this disease. Isolation and characterization studies will utilize the technologies of isoelectric focusing, ion exchange and molecular sieve chromatography, and disc gel electrophoresis, and will be applied independently to investigations of egg granuloma culture superantants and soluble egg products. Purified material will be assayed for activity (1) inducing fibroblast proliferation in diploid dermal fibroblast cultures (2) stimulating collagen synthesis in these cultures and (3) affecting fibroblast chemotaxis in Boyden chambers. In conjunction with studies of collagen synthesis, collagenase activity in granuloma culture supernatants will be measured. In addition to examining the fibroblast-directed activities of the purified molecules derived from the granulomas, these substances will also be tested for (1) macrophage migration inhibition factor, (2) mononuclear cell chemotactic factor, and (3) eosinophil stimulation promotor. Since these activities have previously been shown to be elaborated by granuloma cultures, it is of interest to know whether one or two molecules are responsible for a multiplicity of cellular activations, or whether several factors with independent functions are elaborated. Th ultimate goal of this line of investigation is to develop strategies for prevention or treatment of hepatic fibrosis based upon an understnading of the immunology and cell biology of fibroblast activation in this system.